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Study Sheds Light on Painkillers' Heart Risk
Date:11/3/2008

Cox-2 drugs, like Celebrex, less safe than Cox-1 drugs, like naproxen, study says

MONDAY, Nov. 3 (HealthDay News) -- The increased risk of heart attack that comes with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to treat arthritis pain is directly related to the specific pain-causing molecule they act against, a new study finds.

"We found a significant correlation between the degree of inhibition in vitro [in the laboratory] of whole blood cox-2, but not whole blood cox-1," said the report by researchers in Spain and Italy.

Cox-1 and cox-2 are different forms of cyclooxygenase, an enzyme whose activity increases inflammation and pain. Older NSAIDs, such as ibuprofen and naproxen, act primarily against cox-1. A newer generation of NSAIDs that act against cox-2 reduce the gastrointestinal bleeding, pain and inflammation that are major side effects of the cox-1 drugs, but they have been found to increase the risk of heart attack and stroke.

Three cox-2 inhibitor NSAIDs have been marketed in the United States. Two of them -- Bextra and Vioxx -- were withdrawn from the market earlier this decade because of their association with an increased risk of heart attack and stroke. A third cox-2, Celebrex, remains available, but with a label warning of cardiovascular risk.

All NSAIDs increase heart risk, according to the new study of 8,852 people who had heart attacks. And the increase was related to both the dosage and the length of time the drugs were taken. But the risk was increased by 18 percent by drugs acting primarily against cox-1, compared to a 60 percent increase for those with the greatest cox-2 activity.

The findings were published in the Nov. 11 issue of the Journal of the American College of Cardiology.

Dr. Michael E. Farkouh, director of clinical trials at the Mount Sinai Cardiovascular Institute in New York City, said the new study "lends support to the theory t
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